Professor Jane Salmon
Certolizumab pegol significantly reduces adverse pregnancy outcomes in women with antiphospholipid syndrome (APS) and lupus anticoagulant, the ARA ASM has heard.
Rheumatologist Professor Jane Salmon, from the Hospital for Special Surgery in New York, told the meeting that while she wasn’t recommending its use off label, she did expect it would be approved eventually.
It offered a step forward from usual care which was based solely on preventing thrombosis with prophylactic treatment such as low dose aspirin and low molecular weight heparin.
Professor Salmon, who presented virtually, described decades of preclinical and clinical work on predictors of pregnancy outcomes in patients with lupus and/or APS, including the NIH-funded PROMISSE study.
She said the study identified complement as a predictor of adverse pregnancy outcomes complications in patients with antiphospholipid antibodies and/or SLE.
However back in the lab, the evidence suggested something else was happening in the placenta that was complement dependent and led to an increase in TNF alpha. As well, TNF depletion protected against antiphospholipid antibody-mediated fetal loss and growth restriction.
The preclinical work underpinned the phase 2 IMPACT trial of early administration of TNF inhibitor certolizumab pegol, in addition to standard treatment, in pregnant patients with APS and lupus anticoagulant.
In the single-arm, open-label study of 51 high-risk patients with clinical manifestations of APS from Canada and the US, certolizumab was administered from gestational week 8 through to 28. Six patients experienced an early pregnancy loss at <10 weeks gestation and were excluded from the study. One of the remaining patients was unable to comply with the study regimen and only received four doses of certolizumab.
By definition, most women (>80%) had a history of fetal deaths, pre-eclampsia or placental insufficiency requiring delivery <34 wk gestation, and other adverse pregnancy outcomes in a previous pregnancy.
Professor Salmon said outcomes in the study were compared to the women’s most recent pregnancy and to historical controls from the PROMISSE study who would have been eligible for IMPACT.
The study found that adverse pregnancy outcomes were 20% compared to 44% in the historical controls observed in PROMISSE.
After excluding early pregnancy losses and fetal losses due to lethal genetic abnormalities, live births occurred in 93% of the current pregnancies with all of the infants surviving to hospital discharge.
This compared to just 33% of previous pregnancies resulting in live births and 83% of those infants surviving to discharge (P = 0.0002).
“Since we published the paper… we’ve enrolled seven more patients. Of those patients, one had a primary outcome which was preeclampsia at 33 weeks and six days. So out of the whole 52 patients …what I think is most dramatic is that live births occurred in 49 of the 52 patients,” she said.
“IMPACT shows that certolizumab appears to be effective in preventing placenta-mediated adverse outcomes in high-risk APS patients.”
The study found no safety signals related to certolizumab such as serious maternal or neonatal infections or new onset or flare of SLE.
Professor Salmon said when her team started this body of work 25 years ago, the idea of giving a biologic to a pregnant patient was ‘dogma-challenging’ and very stressful for the regulators.
“I think we showed them that it can work, it can be safe if it’s done thoughtfully, and it can potentially make a difference. It shows that we can protect women and their children through research; we shouldn’t protect them from research.”
IMPACT was published last year in the Annals of Rheumatic Diseases [link here]. The study was part-funded by biopharmaceutical company UCB.